It is our hypothesis that the loss of immune function seen in advanced age in man is due to a failure in normal lymphocyte maturation that leads to an accumulation of immature lymphocytes and that the failure in maturation of T lymphocytes is a delayed result of thymic involution and loss of thymic hormone. We further propose that general mechanisms of the aging process, which may result in decline in proliferative capacity of all cells including lymphocytes, are at most a minor component of decline in immune function and that observed changes in immune regulation are a secondary, rather than a primary, cause of the decline in immune response capacity in the elderly. The tests of these hypotheses rely on two basic experimental techniques; determination of functional parameters of lymphocyte proliferative responses in vitro, and characterisation of lymphocyte differentiation by enzyme markers and cell density. The tests lead to five specific aims: 1) Characterisation of the immature T lymphocyte population in the peripheral blood of aging man. 2) Demonstration that non-lymphocyte specific change in proliferative capacity is not a significant factor in decline of T cell mediated immunity. 3) Demonstration that the failure in T cell maturation is a direct result of loss of thymic hormone in the elderly. 4) Demonstration that changes in immune regulation are a secondary result of the maturation defect. 5) Correlation of lymphocyte function and maturation with increasing age and with survival in individuals of advanced age. The proposed studies combine work in the fields of immunology, cell biology and human biochemistry. We hope to be able to show that the defect in immune function with aging is compatible with the idea of "planned obsolescence" in immunity resulting from loss of thymic function. This demonstration would mean that the immunologic component of the aging process may be amenable to specific intervention in the immune response mechanism. Thus, we ultimately hope to be able to ameliorate the features of the aging process where immunity plays a role, such as, susceptibility to autoimmune disorders, overwhelming infection and perhaps even cancer.